Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II.

Crespo-Leiro, Maria G; Stypmann, Jörg; Schulz, Uwe; Zuckermann, Andreas; Mohacsi, Paul; Bara, Christoph; Ross, Heather; Parameshwar, Jayan; Zakliczyński, Michal; Fiocchi, Roberto; Hoefer, Daniel; Colvin, Monica; Deng, Mario C; Leprince, Pascal; Elashoff, Barbara; Yee, James P; Vanhaecke, Johan (2016). Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II. European Heart Journal, 37(33), ehv682. Oxford University Press 10.1093/eurheartj/ehv682

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AIMS A non-invasive gene-expression profiling (GEP) test for rejection surveillance of heart transplant recipients originated in the USA. A European-based study, Cardiac Allograft Rejection Gene Expression Observational II Study (CARGO II), was conducted to further clinically validate the GEP test performance. METHODS AND RESULTS Blood samples for GEP testing (AlloMap(®), CareDx, Brisbane, CA, USA) were collected during post-transplant surveillance. The reference standard for rejection status was based on histopathology grading of tissue from endomyocardial biopsy. The area under the receiver operating characteristic curve (AUC-ROC), negative (NPVs), and positive predictive values (PPVs) for the GEP scores (range 0-39) were computed. Considering the GEP score of 34 as a cut-off (>6 months post-transplantation), 95.5% (381/399) of GEP tests were true negatives, 4.5% (18/399) were false negatives, 10.2% (6/59) were true positives, and 89.8% (53/59) were false positives. Based on 938 paired biopsies, the GEP test score AUC-ROC for distinguishing ≥3A rejection was 0.70 and 0.69 for ≥2-6 and >6 months post-transplantation, respectively. Depending on the chosen threshold score, the NPV and PPV range from 98.1 to 100% and 2.0 to 4.7%, respectively. CONCLUSION For ≥2-6 and >6 months post-transplantation, CARGO II GEP score performance (AUC-ROC = 0.70 and 0.69) is similar to the CARGO study results (AUC-ROC = 0.71 and 0.67). The low prevalence of ACR contributes to the high NPV and limited PPV of GEP testing. The choice of threshold score for practical use of GEP testing should consider overall clinical assessment of the patient's baseline risk for rejection.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Mohacsi, Paul

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0195-668X

Publisher:

Oxford University Press

Language:

English

Submitter:

Alessandra Witsch

Date Deposited:

23 Mar 2016 09:51

Last Modified:

08 Sep 2017 10:54

Publisher DOI:

10.1093/eurheartj/ehv682

PubMed ID:

26746629

Uncontrolled Keywords:

AlloMap; Heart transplant; Molecular diagnostics; Organ rejection; Rejection surveillance; Tests

BORIS DOI:

10.7892/boris.76635

URI:

https://boris.unibe.ch/id/eprint/76635

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